1. Field of the Invention
The disclosure relates to topical compositions for treating skin conditions associated with aging. More specifically, the invention includes compositions comprising estradiol, estriol, hyaluronic acid, green tea extract, and optionally ascorbic acid for topical administration to the skin. Also included within the scope of the invention are methods of ameliorating symptoms of skin aging including wrinkles, sun damage, rhytids, skin discoloration, rosacea, photoaging, hyperpigmentation, melasma, facial skin tightening including eyelids and jowls, and keratosis. Compositions and methods for improving the aesthetics of scars and promoting wound healing are similarly described. A composition and method for improving urogenital function is likewise provided.
2. Description of the Related Art
In the sixteenth century, Ponce de Leon searched the Americas in vain for the legendary fountain of youth. Nearly 500 years later, individuals still seek a magic youth potion to minimize the signs of aging. Cosmetic surgery to promote a youthful appearance has become a growth industry. Cosmetic treatments such as botox, collagen injections, chemical peels, and laser treatment have been embraced by many to reduce the signs of aging. In recent years, cosmeceuticals with potentially anti-aging effects are a booming business, due in part to the aging baby boomer population.
The human skin consists of two layers, the bottom thicker layer (dermis) and the top thinner layer (epidermis). Dermis is the layer which provides the strength, elasticity, and the thickness to the skin. The main cell type of the dermis is the fibroblast, which is responsible for synthesis and secretion of all the dermal matrix components such as collagen, elastin, and glycosaminoglycans. Collagen provides the strength, elastin is responsible for the elasticity, and glycosaminoglycans afford the skin moistness and plumpness.
With aging, the thickness of the dermal layer is reduced and this is believed to be partially responsible for the formation of wrinkles in aging skin. The top layer of human skin or the epidermis which provides the resilience and the barrier properties of the skin, is composed of many different cell types including keratinocytes, melanocytes, and Langerhans cells. Richards et al. reported that estrogen stimulates secretion of a protein, prolactin, by human dermal fibroblast cells and that prolactin then stimulates proliferation of keratinocytes. Richards et al., J. Invest. Dermatol. 106: 1250 (1996).
Estrogens and synthetic compounds which act like estrogens are known to increase the thickness of the dermal layer and to reduce wrinkle formation in the aging skin. The changes in the skin such as skin dryness, loss of skin elasticity and plumpness occurring after menopause, for example, are attributed to the lack of estrogen production. Estrogen therapy prevents or slows down many of the changes associated with skin aging including increasing skin thickness, reduction of wrinkles, increase in the mitotic rate of the epidermis, reduction in the size and activity of the sebaceous gland, reduction in hair growth rate, and stimulation of collagen turnover. See, Creidi et al. Maturitas 19: 211 (1994); Pugliese, Menopausal skin, Skin Inc., March/April: 69-77 (1994).
Incontinence and vulvar and vaginal atrophy have likewise been associated with aging, particularly in post-menopausal women. Stress incontinence is related to weakness of the muscles within the pelvis that provide support for the urethra and the bladder neck. Stress incontinence may be caused by a functional defect or by anatomical defect of the pelvic floor of the tissue or ligaments connecting the vaginal wall with the pelvic muscles. Trauma to pelvic organs or anatomical structures, neurological injury, and some medications may weaken the pelvic function and support. Additionally, women with low estrogen levels may experience stress incontinence due to decreased vaginal muscle tone. Studies have documented that about 50% of all women have occasional incontinence of urine, stool, or flatus requiring medical care or treatment, and as many as 10% have regular incontinence.
Estrogen hormone replacement therapy (HRT) has been used for the chronic treatment of urinary incontinence and vaginal dryness in post-menopausal women. However, poor patient compliance remains problematic and has been noted with HRT because of negative side-effects, such as increased risk of uterine cancer, stroke, heart disease, bloating, increased breast cancer risk, and vaginal bleeding. Non-operative treatment options for patients with incontinence and pelvic support issues can be attempted. But when these exercises fail, surgical repair is often advised. While systemic hormonal therapy remains controversial in the treatment of pelvic floor issues, local target-specific therapy is recognized as efficacious and safe.
Among the many surgical options for incontinence, the introduction into the abdominal cavity of a pubovaginal sling of a synthetic retro-pubic mid-urethral sling has emerged as highly effective. In this procedure, a tape-like material is passed through the pelvic tissue and is positioned around the urethra and the bladder neck, forming a loop located between the urethra and the vaginal wall to create a supportive “hammock” or sling effect. The tape provides an artificial structural support for tissue ingrowth and thereby provides a newly created body tissue supporting means for the urethra. However, there are inherent risks associated with surgery. In addition to the risks associated with anesthesia, surgery also carries the risk of infection at the wound site, problems with wound healing including erosion at the site of sling placement, and potentially excessive bleeding. Additionally, significant post-operative complications have been observed when, for example, synthetic materials are used.
There is a constant need for improved compositions and methods for reducing the signs of skin aging. Moreover, a non-surgical alternative for improving urogenital function would be a boon to medicine.